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• VAX-ID, a novel drug delivery device, allowed for reliable intradermal injections. • The device was rated as easy to use by healthcare professionals. • The dead space volume of 24 µL was below the set volume of 35 µL as defined by EMA. • Piglets of 12 kg were demonstrated to be a good model to mimic human skin. The recent SARS-Cov2 pandemic and mpox health emergency have led to renewed interest in intradermal vaccination due to its dose sparing potential. Indeed, intradermal vaccination is particularly of interest for use in mass vaccination campaigns, pandemic preparedness programs, and/or for vaccines that are expensive or in short supply. Moreover, the rich immune network in the skin makes it an attractive target not only for prophylactic vaccination, but also for therapeutic vaccination, like immunotherapy and (dendritic) cell-based therapies. The aim of the current paper was to provide an overview of preclinical data generated with VAX-ID®, a novel intradermal drug delivery device, to allow assessing it performance, safety and usability. The device can overcome challenges seen with the Mantoux technique whereby the needle needs to be inserted under a shallow angle. Various parameters of VAX-ID® were evaluated, including dead-space volume, dose accuracy, penetration depth & liquid deposit in piglets, as well as usability by healthcare professionals. The device has shown to have a low dead volume and a high dose accuracy. Importantly, the device performed successful injections at a predefined depth into the dermis with a high safety profile as confirmed by visual and histological evaluation in piglets. Moreover, the device was rated as easy to use by healthcare professionals. The combined preclinical performance and usability findings indicate that VAX-ID® can provide reliable, standardized and accurate drug delivery in the dermal layer of the skin with a high ease of use. The device offers a solution for injection of various prophylactic as well as therapeutic vaccines. [ABSTRACT FROM AUTHOR]

Background: Currently, the free-fall method is commonly used for home-based blood sampling, which is impractical, unhygienic and the volume/quality of blood is often sub-optimal. Few existing devices integrate puncturing and collection of whole-blood. Also these often fail to collect larger volumes. To address these needs, we are developing a novel integrated easy-to-use blood-collection device to collect minimum 400-1000 µL of whole blood. Here, we present the user experience (UX) results to identify design, functionality, quality and safety issues of the first prototype of the Collect2Know (C2K) device (figure 1). Methods: In September 2022, four women and six men (5 HIV-PrEP users) were asked to participate in this UX study. A mixed methods research design was used, including a demographic survey, a usability and acceptability survey and a user interview. Participants were asked to use the prototype without help from the researcher while thinking aloud. Results: Acceptability results show a high willingness to use the device in the future (8/10) and to recommend the device to a family member or friend (7/10). All of the participants experienced none or only mild discomfort while using the device. Main usability issues included: incorrect positioning of finger in the device (4/10), difficulties of using the lancet mechanism (5/10), and confusion about waiting time for sufficient blood collection (7/10). Unsuccessful use was caused by unclear instructions, not reading the instructions and only looking at images, inadequate fixation of the finger in the device and difficulty to assess the volume of collected blood. Six participants were able to collect 400 μL or more. Conclusion: The results of the first prototype of the C2K device are promising. A next prototype and user instruction version will be developed to tackle the main issues found during this first UX study. Following an iterative process, a final prototype will be developed and tested when a limited number of usability issues are identified and 80% of the participants collect at least 400 µL of blood. [ABSTRACT FROM AUTHOR]

Simple Summary: In the field of cancer, body fluids such as urine are gaining interest for non-invasive cancer detection and screening. To enable home collection, sample shipment, and sample storage at ambient temperatures, the addition of preservatives is critical. In this study, we evaluated the performance of a recently developed preservative, UAS™, for the preservation of urinary analytes in oncology applications. We demonstrated that UAS™ preserves host cell integrity and cell-free DNA and prevents bacterial overgrowth under conditions encountered with remote collections. Additionally, UAS™ is compatible with commercially available urinary analyte isolation kits. The preservative facilitates urine collection in the comfort and privacy of the patient's home, making cancer screening programs more accessible and lowering the burden on healthcare workers. Liquid biopsy is a revolutionary tool that is gaining momentum in the field of cancer research. As a body fluid, urine can be used in non-invasive diagnostics for various types of cancer. We investigated the performance of UAS™ as a preservative for urinary analytes. Firstly, the need for urine preservation was investigated using urine samples from healthy volunteers. Secondly, the performance of UAS™ was assessed for cell-free DNA (cfDNA) and host cell integrity during storage at room temperature (RT) and after freeze-thaw cycling. Finally, UAS™ was used in a clinical setting on samples from breast and prostate cancer patients. In the absence of a preservative, urinary cfDNA was degraded, and bacterial overgrowth occurred at RT. In urine samples stored in UAS™, no microbial growth was seen, and cfDNA and cellular integrity were maintained for up to 14 days at RT. After freeze-thaw cycling, the preservation of host cell integrity and cfDNA showed significant improvements when using UAS™ compared to unpreserved urine samples. Additionally, UAS™ was found to be compatible with several commercially available isolation methods. [ABSTRACT FROM AUTHOR]

Biomaterial-associated infections are a major healthcare challenge as they are responsible for high disease burden in critically ill patients. In this study, we have developed drug-eluting antibacterial catheters to prevent catheter-related infections. Niclosamide (NIC), originally an antiparasitic drug, was incorporated into the polymeric matrix of thermoplastic polyurethane (TPU) via solvent casting, and catheters were fabricated using hot-melt extrusion technology. The mechanical and physicochemical properties of TPU polymers loaded with NIC were studied. NIC was released in a sustained manner from the catheters and exhibited in vitro antibacterial activity against Staphylococcus aureus and Staphylococcus epidermidis. Moreover, the antibacterial efficacy of NIC-loaded catheters was validated in an in vivo biomaterial-associated infection model using a methicillin-susceptible and methicillin-resistant strain of S. aureus. The released NIC from the produced catheters reduced bacterial colonization of the catheter as well as of the surrounding tissue. In summary, the NIC-releasing hot-melt extruded catheters prevented implant colonization and reduced the bacterial colonization of peri-catheter tissue by methicillin sensitive as well as resistant S. aureus in a biomaterial-associated infection mouse model and has good prospects for preclinical development. [ABSTRACT FROM AUTHOR]

Bacterial infections are a serious healthcare complication in orthopedic and trauma surgery worldwide. Compared to systemic, local antibiotic prophylaxis has been shown to provide a higher antibiotic dose and bioavailability at the bone site with minimum toxic effects. However, there are still not enough biomaterial and antibiotic combinations available for personalized implant sizes for patients. The aim of this study was to develop a bone fixation plate coating made of a composite of poly-ε-caprolactone, hydroxyapatite and halloysite nanotubes loaded with gentamicin sulphate and fabricated via fused filament fabrication 3D printing technology. The mechanical and thermal properties of the biomaterial were analyzed. The in vitro release kinetics of gentamicin sulphate were evaluated for 14 days showing a burst release during the first two days that was followed by a sustained release of bactericidal concentrations. The composite loaded with 2 and 5% gentamicin sulphate exhibited complete antimicrobial killing of Staphylococcus aureus in an ex vivo mouse femur fixation plate infection model. Moreover, a fixation plate of the composite loaded with 5% of gentamicin sulphate was able to prevent S. aureus infection in the bone and surrounding tissue in an in vivo mouse bone fixation plate infection model 3 days post-surgery. In conclusion, the newly developed composite material successfully prevented infection in vivo. Additionally, the ability to use fused filament fabrication 3D printing to produce patient-specific implants may provide a wider range of personalized solutions for patients. [ABSTRACT FROM AUTHOR]

Highlights • HPV DNA detection in FV urine is reliable when using an appropriate preservative, extraction method and PCR-based test. • No difference in HPV DNA concentration was found in FV urine collected in the morning versus later during the day. • Colli-Pee collected samples show higher HPV concentration. However at higher hDNA concentrations, this effect disappeared. Abstract Great interest has been directed towards the use of first-void (FV) urine as a liquid biopsy for high-risk HPV DNA testing. The aim of this study was to investigate the potential effect of a first generation FV urine collection device on the detection of HPV DNA and to assess if the concentration of HPV DNA varies between FV urine collected in the morning and those collected later during the day. In this prospective cohort study, 33 self-reported HPV-positive women participated. An FV urine sample was collected by these women in the morning (first urine of the day) and another sample was collected later that day for four consecutive days using two different collection methods; i.e., the Colli-Pee® and a standard urine cup. Samples were collected at home and returned at ambient temperature to the laboratory by postal mail. HPV DNA testing was conducted with the Riatol qPCR HPV genotyping assay. Based on the combined generalized linear mixed model used, there was no significant impact of the timing of collection (morning versus later during the day) on copies of HPV DNA, whereas Colli-Pee® collected samples show higher HPV concentrations than cup collected samples. However, at high concentrations of hDNA, the benefit of the Colli-Pee® disappeared. [ABSTRACT FROM AUTHOR]

[Display omitted] • The mechanical and rheological properties are limiting steps for FFF. • Increasing the VA content showed lower buckling stress, elastic and flexural modulus. • The inadequate flow during FFF was due to the viscosity variation during extrusion. • DEAM showed formulation freedom as the screw rotation drives the material flow. • In-vitro kinetics was similar between tablets printed from filaments, pellets or powder. Personalized medicine, produced through 3D printing, is a promising approach for delivering the required drug dose based on the patient's profile. The primary purpose of this study was to investigate the potential of two different extrusion-based additive manufacturing techniques – fused filament fabrication (FFF) and screw-based 3D printing, also known as direct extrusion additive manufacturing (DEAM). Different ethylene-vinyl acetate (EVA) copolymers (9 %VA, 12 %VA, 16 %VA, 18 %VA, 25 %VA, 28 %VA, and 40 %VA) were selected and loaded with 50% (w/w) metoprolol tartrate (MPT). Hot-melt extrusion was performed to produce the drug-loaded filaments. These filaments were used for FFF in which the mechanical and rheological properties were rate-limiting steps. The drug-loaded filament based on the 18 %VA polymer was the only printable formulation due to its appropriate mechanical and rheological properties. As for the highest VA content (40 %VA), the feeding pinch rolls cause buckling of the filaments due to insufficient stiffness, while other filaments were successfully feedable towards the extrusion nozzle. However, poor flowability out of the extrusion nozzle due to the rheological limitation excluded these formulations from the initial printing trials. Filaments were also pelletized and used for pellets-DEAM. This method showed freedom in formulation selection because the screw rotation drives the material flow with less dependence on their mechanical properties. All drug-loaded pellets were successfully printed via DEAM, as sufficient pressure was built up towards the nozzle due to single screw extrusion processing method. In contrast, filaments were used as a piston to build up the pressure required for extrusion in filament-based printing, which highly depends on the filament's mechanical properties. Moreover, printing trials using a physical mixture in powder form were also investigated and showed promising results. In vitro drug release showed similar release patterns for MPT-loaded 3D printed tablets regardless of the printing technique. Additionally, pellets-DEAM enabled the production of tablets with the highest VA content, which failed in FFF 3D printing but showed an interesting delayed release profile. [ABSTRACT FROM AUTHOR]

Additive manufacturing is widely used to produce highly complex structures. Moreover, this technology has proven its superiority in producing tools which can be used in different applications. We designed and produced an extrusion nozzle that allowed us to hot melt extrude drug-loaded tubes. The tubes were an essential part of a new mouse ventilator-associated pneumonia (VAP) model. Ciprofloxacin (CPX) was selected for its expected activity against the pathogen Staphylococcus aureus and ease of incorporation into thermoplastic polyurethane (TPU). TPU was selected as the carrier polymer for its biocompatibility and use in a variety of medical devices such as tubing and catheters. The effect of loading CPX within the TPU polymeric matrix and the physicochemical properties of the produced tubes were investigated. CPX showed good thermal stability and in vitro activity in preventing S. aureus biofilm formation after loading within the tube's polymeric matrix. Moreover, the produced tubes showed anti-infective efficacy in vivo. The produced tubes, which were extruded via our novel nozzle, were vital for the validation of our mouse VAP model. This model can be adopted to investigate other antibacterial and antibiofilm compounds incorporated in polymeric tubes using hot melt extrusion. [ABSTRACT FROM AUTHOR]

The potential of first-void (FV) urine as a non-invasive liquid biopsy for detection of human papillomavirus (HPV) DNA and other biomarkers has been increasingly recognized over the past decade. In this study, we investigated whether the volume of this initial urine stream has an impact on the analytical performance of biomarkers. In parallel, we evaluated different DNA extraction protocols and introduced an internal control in the urine preservative. Twenty-five women, diagnosed with high-risk HPV, provided three home-collected FV urine samples using three FV urine collection devices (Colli-Pee) with collector tubes that differ in volume (4, 10, 20 mL). Each collector tube was prefilled with Urine Conservation Medium spiked with phocine herpesvirus 1 (PhHV-1) DNA as internal control. Five different DNA extraction protocols were compared, followed by PCR for GAPDH and PhHV-1 (qPCR), HPV DNA, and HBB (HPV-Risk Assay), and ACTB (methylation-specific qPCR). Results showed limited effects of collection volume on human and HPV DNA endpoints. In contrast, significant variations in yield for human endpoints were observed for different DNA extraction methods (p < 0.05). Additionally, the potential of PhHV-1 as internal control to monitor FV urine collection, storage, and processing was demonstrated. [ABSTRACT FROM AUTHOR]

Additive manufacturing technologies have been widely used in the medical field. More specifically, fused filament fabrication (FFF) 3D-printing technology has been thoroughly investigated to produce drug delivery systems. Recently, few researchers have explored the possibility of directly 3D printing such systems without the need for producing a filament which is usually the feedstock material for the printer. This was possible via direct feeding of a mixture consisting of the carrier polymer and the required drug. However, as this direct feeding approach shows limited homogenizing abilities, it is vital to investigate the effect of the pre-mixing step on the quality of the 3D printed products. Our study investigates the two commonly used mixing approaches—solvent casting and powder mixing. For this purpose, polycaprolactone (PCL) was used as the main polymer under investigation and gentamicin sulfate (GS) was selected as a reference. The produced systems' efficacy was investigated for bacterial and biofilm prevention. Our data show that the solvent casting approach offers improved drug distribution within the polymeric matrix, as was observed from micro-computed topography and scanning electron microscopy visualization. Moreover, this approach shows a higher drug release rate and thus improved antibacterial efficacy. However, there were no differences among the tested approaches in terms of thermal and mechanical properties. [ABSTRACT FROM AUTHOR]

Fused filament fabrication (FFF) 3D printing technology is widely used in many fields. For almost a decade, medical researchers have been exploring the potential use of this technology for improving the healthcare sector. Advances in personalized medicine have been more achievable due to the applicability of producing drug delivery devices, which are explicitly designed based on patients' needs. For the production of these devices, a filament—which is the feedstock for the FFF 3D printer—consists of a carrier polymer (or polymers) and a loaded active pharmaceutical ingredient (API). This systematic review of the literature investigates the most widely used approaches for producing drug-loaded filaments. It also focusses on several factors, such as the polymeric carrier and the drug, loading capacity and homogeneity, processing conditions, and the intended applications. This review concludes that the filament preparation method has a significant effect on both the drug homogeneity within the polymeric carrier and drug loading efficiency. [ABSTRACT FROM AUTHOR]